Scientists in Baltimore believe they may have found a way to predict – and eventually improve – survival in people with malignant peritoneal mesothelioma (MPM).
Peritoneal mesothelioma is a rare cancer of the membranes that line the abdominal cavity. Like other forms of mesothelioma, it is caused by exposure to fibers of the mineral asbestos. While it is almost always fatal, people with peritoneal mesothelioma tend to exhibit very different responses to the disease. Writing in the journal Cancer, the Maryland researchers note, “There is marked variability in its clinical behavior. Some patients die rapidly, and others survive for many years.”
The researchers set out to determine reasons for this variability and believe the answer may lie in signaling pathways that tell cancer cells to grow and proliferate. Experimenting on tumor samples from 41 mesothelioma patients, the researchers analyzed the genes expressed by each set of cells. What they found was an important difference in the ‘signaling chemicals’ that are responsible for protein synthesis and RNA production inside cells.
In one group, the signaling pathways known as Phosphoinositide-3-kinase (PI3K) and the closely interacting mammalian target of rapamycin (mTOR) were overexpressed. In cases where the genes produced by these pathways were present, the peritoneal mesothelioma patients had survived for a median of 24 months.
But in cases where these pathways, and their corresponding genes, were not found, the mesothelioma patients had a median survival of 69.5 months. To further test their theory that these cell pathways were linked to cancer cell proliferation and prognosis, the researchers used a chemical to inhibit the P13K and mTOR pathways in cell samples. They found that, when these pathways were inhibited, cell signaling and cell proliferation were significantly reduced.
Taken together, the researchers conclude that these two experiments point to the value of analyzing gene expression pathways in patients diagnosed with malignant peritoneal mesothelioma. They write, “Targeting the PI3K and mTOR signaling pathways may have significant therapeutic value in patients with MPM.”
The study was conducted by the Division of Surgical Oncology at the University of Maryland School of Medicine in Baltimore and will be published in an upcoming issue of Cancer.
Varghese, S et al. “Activation of the phosphoinositide-3-kinase and mammalian target of rapamycin signaling pathways are associated with shortened survival in patients with malignant peritoneal mesothelioma”, September 13, 2010. Epub ahead of print.
Park, Sophie et al, “Role of the PI3K/AKT and mTOR signaling pathways in acute myeloid leukemia”, November 30, 2009. Haematologica, Vol 95, Issue 5, 819-828